The incidence of heroin abuse has been increasing steadily over the past few years, and will most likely continue to increase, with non-injection routes becoming more popular. Although treatment medications (such as methadone, levo-alpha-acetylmethadol (LAAM), and naltrexone) for opiate dependence currently exist, many problems are associated with their use such as patient noncompliance, continued opiate use during treatment, and high relapse rates during withdrawal from treatment. Several possible causes for these problems have been suggested but insufficient research has been conducted to evaluate the effects of these medications on ongoing human behavior in a research laboratory setting. In the proposed research, opiate-dependent male and female subjects residing in a controlled setting will be given the opportunity to work for smoked heroin or money in both the presence and absence of a treatment medication. These studies will examine the multiplicity of ways in which these medications affect ongoing human behavior including effects on heroin consumption, performance, mood, social behavior, food consumption, physiological measures, tobacco and caffeine consumption, and subjects' verbal reports of drug effects. The model thus developed will be used to evaluate potential new medications for opiate abuse as they are developed and before they are put into time consuming and expensive multi-center trials. The specific aims of the proposal are: 1) the development of a model of smoked heroin self-administration in humans under controlled conditions to evaluate patterns of heroin self-administration, as well as doses of heroin that are used; 2) an analysis of the similarities and differences between i.v. and smoked heroin on physiological, subjective- effects, and performance measures; 3) the development of a model for evaluating both existing and potential new treatment medications on heroin self-administration, as well as other ongoing behaviors; 4) evaluation of whether narcotic antagonists, at the doses that are currently used, are effective with the newly potent street heroin; and 5) development and validation of this model for the evaluation of potential new medications in an efficient and safe fashion.